Pizova Klara, Bajgar Robert, Fillerova Regina, Kriegova Eva, Cenklova Vera, Langova Katerina, Konecny Petr, Kolarova Hana
Department of Medical Biophysics, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 3, 775 15 Olomouc, Czech Republic; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 5, 77900 Olomouc, Czech Republic.
Department of Medical Biophysics, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 3, 775 15 Olomouc, Czech Republic; Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Hnevotinska 5, 77900 Olomouc, Czech Republic.
J Photochem Photobiol B. 2015 Jan;142:186-96. doi: 10.1016/j.jphotobiol.2014.12.003. Epub 2014 Dec 9.
Photodynamic therapy (PDT) is based on the tumor-selective accumulation of photosensitizer followed by irradiation with light of an appropriate wavelength. After irradiation and in the presence of oxygen, photosensitizer induces cellular damage. The aim of this study was to evaluate effects of two photosensitizers TMPyP and ClAlPcS2 on cell lines to obtain better insight into their mechanisms of action. We determined cell viability, reactive oxygen species (ROS) generation and changes in expression levels of two important early response genes, C-MYC and C-FOS, on tumor MCF7 (human breast adenocarcinoma) and G361 (human melanoma) cell lines and non-tumor BJ cell line (human fibroblast) after photodynamic reaction with TMPyP and ClAlPcS2 as photosensitizers. In addition TMPyP and ClAlPcS2 cellular uptake and clearance and antioxidant capacity of the mentioned cell lines were investigated. We found appropriate therapeutic doses and confirmed that both tested photosensitizers are photodynamically efficient in treatment used cells in vitro. TMPyP is more efficient; it had higher ROS production and toxicity after irradiation by intermediate therapeutic doses than ClAlPcS2. We revealed that both TMPyP and ClAlPcS2-PDT increased C-FOS expression on tumor cell lines (G361 and MCF7), but not on non-tumor BJ cell line. Conversely, both TMPyP and ClAlPcS2-PDT decreased C-MYC expression on non-tumor BJ cell line but not on tumor cell lines. As first we tested these photosensitizers in such extent and we believe that it can help to better understand mechanisms of PDT and increase its efficiency and applicability.
光动力疗法（PDT）基于光敏剂在肿瘤中的选择性蓄积，随后用适当波长的光进行照射。照射后且在有氧存在的情况下，光敏剂会诱导细胞损伤。本研究的目的是评估两种光敏剂四甲基吡啶卟啉（TMPyP）和二氯铝酞菁磺酸盐（ClAlPcS2）对细胞系的作用，以更好地了解它们的作用机制。我们测定了以TMPyP和ClAlPcS2作为光敏剂进行光动力反应后，肿瘤MCF7（人乳腺腺癌）细胞系、G361（人黑色素瘤）细胞系和非肿瘤BJ细胞系（人成纤维细胞）的细胞活力、活性氧（ROS）生成以及两个重要早期反应基因C-MYC和C-FOS表达水平的变化。此外，还研究了TMPyP和ClAlPcS2在上述细胞系中的细胞摄取和清除情况以及抗氧化能力。我们找到了合适的治疗剂量，并证实两种受试光敏剂在体外对所用细胞的光动力治疗中均有效。TMPyP更有效；在中等治疗剂量照射后，它比ClAlPcS2产生更高的ROS且毒性更大。我们发现TMPyP和ClAlPcS2介导的光动力疗法（PDT）均能增加肿瘤细胞系（G361和MCF7）中C-FOS的表达，但对非肿瘤BJ细胞系无此作用。相反，TMPyP和ClAlPcS2介导的PDT均能降低非肿瘤BJ细胞系中C-MYC的表达，但对肿瘤细胞系无此作用。我们首次在这样的范围内测试了这些光敏剂，并且相信这有助于更好地理解PDT的机制并提高其效率和适用性。
